This proposal consists of research focused on: 1) the central neurochemical organization of sensory neurons that triggers integrated respiratory responses to changes in CO2/H+, 2) the receptor systems of these neurons, activation of which may modulate their response to CO2/H+ signal, and 3) their connectivity with respiratory output neurons such as hypoglossal motor cells. Recently, it has been shown that expression of immediate-early genes are sensitive, inducible, and broadly applicable markers for neurons activated by extracellular stimuli. In the proposed studies, we will use expression of c-fos gene encoded protein (cFos) to identify neurons activated by hypercapnia, in order to investigate neurotransmitter content and receptor systems of these cells. The connectivity of chemosensory neurons with the respiratory-related motoneuron pools will be determined by combining retrograde tracer technique with cFos immunohistochemistry. The data derived from these studies will provide basic information related to the central chemosensory network, neurochemical organization, and chemical nature of communications between chemosensitive ells and brainstem output neurons. These results will have indirect bearing on the understanding of neurochemical mechanisms underlying centrally mediated respiratory and cardiovascular dysfunctions, as might occur in idiopathic alveolar hypoventilation, sleep apnea and sudden infant death syndrome.